dbSNP rs201145362: POU2F3:p.Ala149Val (chr11-120305031-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_014352.4(POU2F3):c.446C>T(p.Ala149Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000329 in 1,599,614 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 27)

Exomes 𝑓: 0.00035 ( 1 hom. )

Consequence

POU2F3
NM_014352.4 missense, splice_region

Scores

Splicing: ADA: 0.9792

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.78

Publications

4 publications found

Variant links:

Genes affected

POU2F3 (HGNC:19864): (POU class 2 homeobox 3) This gene encodes a member of the POU domain family of transcription factors. POU domain transcription factors bind to a specific octamer DNA motif and regulate cell type-specific differentiation pathways. The encoded protein is primarily expressed in the epidermis, and plays a critical role in keratinocyte proliferation and differentiation. The encoded protein is also a candidate tumor suppressor protein, and aberrant promoter methylation of this gene may play a role in cervical cancer. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

POU2F3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014352.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU2F3	NM_014352.4	MANE Select	c.446C>T	p.Ala149Val	missense splice_region	Exon 7 of 13	NP_055167.2	Q9UKI9-1
	POU2F3	NM_001244682.2		c.452C>T	p.Ala151Val	missense splice_region	Exon 7 of 13	NP_001231611.1	Q9UKI9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
POU2F3	ENST00000543440.7	TSL:1 MANE Select	c.446C>T	p.Ala149Val	missense splice_region	Exon 7 of 13	ENSP00000441687.2	Q9UKI9-1
POU2F3	ENST00000533620.5	TSL:1	n.*112C>T		splice_region non_coding_transcript_exon	Exon 8 of 14	ENSP00000435738.2	E9PIN6
POU2F3	ENST00000533620.5	TSL:1	n.*112C>T		3_prime_UTR	Exon 8 of 14	ENSP00000435738.2	E9PIN6

Frequencies

GnomAD3 genomes

AF:

0.000141

AC:

AN:

148590

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000500

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000281

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000246

AC:

AN:

248370

AF XY:

0.000261

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000518

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000348

AC:

505

AN:

1451024

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

230

AN XY:

721718

show subpopulations

African (AFR)

AF:

0.0000601

AC:

AN:

33296

American (AMR)

AF:

0.0000454

AC:

AN:

44030

Ashkenazi Jewish (ASJ)

AF:

0.0000389

AC:

AN:

25722

East Asian (EAS)

AF:

0.00

AC:

AN:

39674

South Asian (SAS)

AF:

0.00

AC:

AN:

84736

European-Finnish (FIN)

AF:

0.0000189

AC:

AN:

52842

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5670

European-Non Finnish (NFE)

AF:

0.000438

AC:

484

AN:

1105316

Other (OTH)

AF:

0.000251

AC:

AN:

59738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

117

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000141

AC:

AN:

148590

Hom.:

Cov.:

AF XY:

0.0000832

AC XY:

AN XY:

72146

show subpopulations

African (AFR)

AF:

0.0000500

AC:

AN:

40006

American (AMR)

AF:

0.00

AC:

AN:

14774

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

5100

South Asian (SAS)

AF:

0.00

AC:

AN:

4686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9766

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.000281

AC:

AN:

67564

Other (OTH)

AF:

0.00

AC:

AN:

2030

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000354

Hom.:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000305

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.15

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.79

M_CAP

Benign

0.010

MetaRNN

Benign

0.17

MetaSVM

Uncertain

0.019

MutationAssessor

Benign

2.0

PhyloP100

5.8

PrimateAI

Uncertain

0.65

REVEL

Uncertain

0.34

Sift4G

Uncertain

0.051

Polyphen

0.84

Vest4

0.29

MVP

0.72

MPC

0.65

ClinPred

0.63

GERP RS

6.2

Varity_R

0.19

gMVP

0.58

Mutation Taster

=66/34

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over